scholarly journals Association of B‐cell lymphoma 2/microRNA‐497 gene expression ratio score with metastasis in patients with colorectal cancer: A propensity‐matched cohort analysis

Author(s):  
Shahad W. Kattan ◽  
Yahya H. Hobani ◽  
Nouf Abubakr Babteen ◽  
Saleh A. Alghamdi ◽  
Eman A. Toraih ◽  
...  
Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1392-1392 ◽  
Author(s):  
Pareen J. Shenoy ◽  
Kevin Bumpers ◽  
Nassoma King ◽  
Taoying Huang ◽  
Neha Malik ◽  
...  

Abstract Abstract 1392 Poster Board I-414 Background: While African-Americans have a lower incidence of diffuse large B-cell lymphoma (DLBCL) than Whites (W) in the United States, there appear to be racial differences in clinical features, the use of chemoimmunotherapy(Flowers, AACR 2008), and treatment outcomes. However, previous analyses have been hampered by limited numbers of Black (B) patients (pts); lack of direct clinical information on pathology, prognostic factors, treatment, and outcomes; limited follow-up; or all three. Methods: To examine B/W differences in the use of CHOP-based chemotherapy vs. rituximab CHOP (RCHOP), we performed a retrospective, matched cohort analysis comparing the impact of race, on presenting features, treatment, and outcomes in a clinical setting with detailed data ascertainment from pathology, clinical, and pharmacy records. Patients diagnosed with DLBCL from 1981 to 2009 were identified from Emory pathology and medical records using previously published methods (Graiser, Cancer Informatics 2007). Baseline demographic data, components of the International Prognostic Index (IPI: age, performance status, lactate dehydrogenase [LDH], number of extranodal sites involved, stage), insurance status, employment status, treatment and survival data were extracted. Differences by race in baseline features and treatment category (CHOP vs. RCHOP) were analyzed using Chi-squared statistical analysis. Univariate and multivariate logistic regression analyses were performed for the entire population and cohorts matched by IPI, age, and year of diagnosis, to determine predictors of RCHOP use, 2-year and 5-year overall survival (OS). Cox regression was used to analyze the predictors of OS. Results: A total of 531 (348 W and 107 B) pts with a confirmed diagnosis of DLBCL were identified. The median age of diagnosis for B was significantly less than that for W pts (median age 46 (range: 18–87) vs. 56 (range: 18–86), respectively; p<0.001). There were no differences in stage, performance status or extranodal disease, but B pts more frequently presented with elevated LDH (50% vs. 37%, p=0.04). There were no racial differences in RCHOP use. Pts who had elevated LDH were more likely to receive RCHOP (p<0.001). W race was a predictor of improved 2yr OS. W race, early stage, IPI <2 were predictors of improved 5yr OS. However, there were no B/W differences in OS, in the CHOP cohort or the RCHOP cohort. After matching for revised IPI group, age at diagnosis, and diagnosis year B (n=104) and W (n=104) pts had similar rates of RCHOP use (41% vs. 46%), 2-yr OS, and 5-yr OS. Conclusions: These data corroborate findings that B pts present with DLBCL at a younger age. In the setting of a single institution referral center with detailed ascertainment of treatment, there do not appear to be racial differences in RCHOP use or outcomes. Since IPI, age, and year of treatment may influence treatment selection and outcomes, matching cohorts on these factors is necessary when examining B/W differences. Disclosures: Flowers: Amos Medical Faculty Development Program grant from the American Society of Hematology/Robert Wood Johnson Foundation: Research Funding.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Selin Merdan ◽  
Kritika Subramanian ◽  
Turgay Ayer ◽  
Johan Van Weyenbergh ◽  
Andres Chang ◽  
...  

AbstractThe clinical risk stratification of diffuse large B-cell lymphoma (DLBCL) relies on the International Prognostic Index (IPI) for the identification of high-risk disease. Recent studies suggest that the immune microenvironment plays a role in treatment response prediction and survival in DLBCL. This study developed a risk prediction model and evaluated the model’s biological implications in association with the estimated profiles of immune infiltration. Gene-expression profiling of 718 patients with DLBCL was done, for which RNA sequencing data and clinical covariates were obtained from Reddy et al. (2017). Using unsupervised and supervised machine learning methods to identify survival-associated gene signatures, a multivariable model of survival was constructed. Tumor-infiltrating immune cell compositions were enumerated using CIBERSORT deconvolution analysis. A four gene-signature-based score was developed that separated patients into high- and low-risk groups. The combination of the gene-expression-based score with the IPI improved the discrimination on the validation and complete sets. The gene signatures were successfully validated with the deconvolution output. Correlating the deconvolution findings with the gene signatures and risk score, CD8+ T-cells and naïve CD4+ T-cells were associated with favorable prognosis. By analyzing the gene-expression data with a systematic approach, a risk prediction model that outperforms the existing risk assessment methods was developed and validated.


PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0208709 ◽  
Author(s):  
Silvia Da Ros ◽  
Luca Aresu ◽  
Serena Ferraresso ◽  
Eleonora Zorzan ◽  
Eugenio Gaudio ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0250013
Author(s):  
Chia-Hsin Hsu ◽  
Hirotaka Tomiyasu ◽  
Chi-Hsun Liao ◽  
Chen-Si Lin

Doxorubicin resistance is a major challenge in the successful treatment of canine diffuse large B-cell lymphoma (cDLBCL). In the present study, MethylCap-seq and RNA-seq were performed to characterize the genome-wide DNA methylation and differential gene expression patterns respectively in CLBL-1 8.0, a doxorubicin-resistant cDLBCL cell line, and in CLBL-1 as control, to investigate the underlying mechanisms of doxorubicin resistance in cDLBCL. A total of 20289 hypermethylated differentially methylated regions (DMRs) were detected. Among these, 1339 hypermethylated DMRs were in promoter regions, of which 24 genes showed an inverse correlation between methylation and gene expression. These 24 genes were involved in cell migration, according to gene ontology (GO) analysis. Also, 12855 hypermethylated DMRs were in gene-body regions. Among these, 353 genes showed a positive correlation between methylation and gene expression. Functional analysis of these 353 genes highlighted that TGF-β and lysosome-mediated signal pathways are significantly associated with the drug resistance of CLBL-1. The tumorigenic role of TGF-β signaling pathway in CLBL-1 8.0 was further validated by treating the cells with a TGF-β inhibitor(s) to show the increased chemo-sensitivity and intracellular doxorubicin accumulation, as well as decreased p-glycoprotein expression. In summary, the present study performed an integrative analysis of DNA methylation and gene expression in CLBL-1 8.0 and CLBL-1. The candidate genes and pathways identified in this study hold potential promise for overcoming doxorubicin resistance in cDLBCL.


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